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| ID | Type | Description | Link |
|---|---|---|---|
| 23-008241 | Other Identifier | Mayo Clinic Institutional Review Board |
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This early phase I trial tests the safety, side effects and how well medication combinations of dasatinib, quercetin, fisetin, temozolomide, LMP744, and autologous tumor lysate particle only (TLPO) vaccine work in treating patients with glioma for which the patient has received treatment in the past (previously treated) and for tumor cells that remain after attempts to treat the tumor have been made (residual disease). Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply, which may help keep tumor cells from growing. Quercetin and fisetin are compounds found in plants. They have antioxidant and anti-inflammatory properties and help remove senescent cells, older or damaged cells that have stopped dividing but don't die off as they should and build up in tissues over time. Senescent cells may cause inflammation or damage to nearby healthy cells. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells and slow down or stop tumor growth. LMP744 works by interfering with a protein that tumor cells use to copy and repair their DNA. By blocking this repair process, the drug causes DNA damage so that tumor cells cannot survive. The autologous TLPO vaccine is made using material from a patient's own tumor. It delivers the tumor material to immune cells so they can learn to recognize and attack the cancer. Giving medication combinations of dasatinib, quercetin, fisetin, temozolomide, LMP744, and autologous TLPO vaccine may be safe, tolerable and/or effective in treating patients with previously treated glioma with residual disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Regimen 1 (1 cycle rest, assignment to treatment regimen) | Active Comparator | Patients receive rest and take no treatment on days 1-35 of cycle 1. At the end of cycle 1, patients may proceed to regimens 2, 3, 4, 5, 6, 7, or 8. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study. |
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| Regimen 2 (dasatinib, quercetin) | Experimental | Patients receive dasatinib PO QD on days 1-2 and quercetin PO QD on days 1-2 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study. |
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| Regimen 3 (fisetin) | Experimental | Patients receive fisetin PO QD on days 1-2 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Biospecimen Collection | Procedure | Undergo blood sample collection |
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| Measure | Description | Time Frame |
|---|---|---|
| Completion of 3 cycles | Will evaluate feasibility of serially screening multiple candidate therapies or combinations based on individualized empiric biological feedback from biospecimens and imaging. This will be measured as the percentage of patients successfully completing 3 cycles of drug administration (study visits). A cycle is 35 +/- 7 days. Regimen will be considered feasible if at least 2/3 of patients can achieve this target. | Up to 16 weeks |
| Turnaround time for scan and marker data | Will also evaluate feasibility as the turnaround time for scan and marker data that is used to determine if patients should stay on current therapy or move to the next regimen. The outcomes will be cycle-specific. A cycle is 35 +/- 7 days. The target for this is a mean turnaround time of 3 days; if the maximum turnaround time exceeds 5 days, this will prompt an evaluation of process to identify barriers. | Up to 16 weeks (completion of 3 cycles) |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events | Will assess the safety of this algorithm-based approach to individualized therapeutic drug combinations in patients with pre-recurrent central nervous system tumors. The study drugs will be considered well-tolerated with no grade 3 or higher adverse event attributable to the drugs in the 10 patients. Adverse events will be evaluated per the Common Terminology Criteria for Adverse Events (CTCAE) version 5 criteria and summarized by type and severity as well as perceived attribution to study treatment for each of the regimens received by patients. |
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Inclusion Criteria - Treatment Arm (Regimens 1-8):
Age ≥ 18 years
Prior diagnosis of a glioma treated with chemotherapy and/or radiation with stable disease based on Response Assessment in Neuro-Oncology (RANO) criteria
Must have IDH-mutant OR MGMT-methylated glioma
Eastern Cooperative Oncology Group (ECOG) of 0, 1, or 2, and Karnofsky performance status >= 50
Hemoglobin ≥ 9.0 g/dL (≤ 15 days prior to registration)
Absolute neutrophil count (ANC) ≥ 1500/mm^3 (≤ 15 days prior to registration)
Platelet count ≥ 100,000/mm^3 (without transfusion ≤ 7 days preceding lab assessment) (≤ 15 days prior to registration)
Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN) (or ≤ 5 x ULN for patients with liver involvement) (≤ 15 days prior to registration)
Calculated creatinine clearance ≥ 45 ml/min using the Cockcroft-Gault formula (≤ 15 days prior to registration)
Average corrected QT interval (QTc) ≤ 450 ms on triplicate 12 lead electrocardiogram (ECG) ≤ 29 days prior to registration
Negative serum pregnancy test is required for persons of childbearing potential ≤ 8 days prior to registration
Presence of an implanted cranial CSF access device, such as Ommaya reservoir or ventriculoperitoneal shunt
Willingness to provide blood and CSF samples for research
Co-enrollment on the neuro-oncology biorepository [institutional review board (IRB) 12-003458] for collection of research blood and CSF samples
Provide written informed consent
Willingness to return to Mayo Clinic for follow-up
Inclusion Criteria - Monitoring Arm (Regimen 1 only):
Exclusion Criteria - Treatment Arm (Regimens 1-8):
Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
Patients who are not appropriate medical candidates due to current or past medical history or uncontrolled concurrent illness which limits safety of or compliance to study proceedings
Participants who are unable to swallow tablets or who are at risk for impaired absorption of oral medication
Patients with known hypersensitivity or allergy to all of the study drugs on the protocol (known hypersensitivity or allergy to one drug does not preclude participation in this protocol)
Inability to undergo MRI scans
Exclusion Criteria - Monitoring Arm (Regimen 1 only):
Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
Current or past medical history or uncontrolled concurrent illness which limits safety or compliance with study proceedings
Known hypersensitivity or allergy to radioactive tracers
Inability to undergo clinical imaging
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trials Referral Office | Contact | 855-776-0015 | mayocliniccancerstudies@mayo.edu |
| Name | Affiliation | Role |
|---|---|---|
| Terence C. Burns, MD, PhD | Mayo Clinic in Rochester | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic in Rochester | Recruiting | Rochester | Minnesota | 55905 | United States |
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| Label | URL |
|---|---|
| Mayo Clinic Clinical Trials | View source |
| Review article discussing the rationale for and general design of this study | View source |
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| Regimen 4 (temozolomide) | Experimental | Patients receive temozolomide PO QD on days 1-5 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study. |
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| Regimen 5 (dasatinib, quercetin, temozolomide) | Experimental | Patients receive temozolomide PO QD on days 1-5, quercetin PO QD days 14-15 and dasatinib PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study. |
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| Regimen 6 (fisetin, temozolomide) | Experimental | Patients receive temozolomide PO QD on days 1-5 and fisetin PO QD on days 14-15 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study. |
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| Monitoring Arm | Experimental | Patients take no treatment and undergo monitoring only. Patients receive rest as in Regimen 1 and do not proceed to any treatment on study. Patients undergo MRI throughout the study as well as undergo blood and CSF sample collection on study. Patients may undergo amino acid PET scans on study. |
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| Regimen 7 (LMP744) | Experimental | Patients receive LMP744 IV over 1 hour on days 1-5 of each cycle. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study. |
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| Regimen 8 (autologous TLPO vaccine) | Experimental | Patients receive autologous TLPO vaccine ID on day 1 of cycles 1-3 and cycles 6, 9, and 12. Cycles repeat every 35 days in the absence of disease progression or unacceptable toxicity. Patients without a PR or CR on imaging at the end of cycle 1 may proceed to another regimen. NOTE: Patients may continue receiving autologous TLPO vaccine after proceeding to another regimen. Patients with a PR or CR may remain on the current regimen. Additionally, patients undergo MRI throughout the study as well as undergo blood sample collection on study. Patients may undergo amino acid PET scans on study. |
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| Dasatinib | Drug | Given PO |
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| Fisetin | Drug | Given PO |
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| Magnetic Resonance Imaging | Procedure | Undergo MRI |
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| Patient Observation | Other | Receive rest and take no treatment |
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| Positron Emission Tomography | Procedure | Undergo amino acid PET scan (optional) |
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| Quercetin | Drug | Given PO |
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| Temozolomide | Drug | Given PO |
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| Topoisomerase-1 Inhibitor LMP744 | Drug | Given IV |
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| Single Agent Therapy | Drug | Given autologous TLPO vaccine ID |
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| Up to 3 years |
| Change in senescence-associated proteins | Will evaluate relative change from baseline in enrichment for a panel of senescence-associated proteins in cerebrospinal fluid (CSF) for each sequentially administered senolytic agent. An effective senolytics regimen will decrease CSF senescence associated secretory phenotype, including monocyte chemoattractant protein-1 levels, by at least 25%. | Baseline; up to 3 years |
| Cell-free mitochondrial deoxyribonucleic acid (DNA) | Will evaluate the percentage change in cell-free mitochondrial DNA. An effective senolytics regimen will decrease cell-free mitochondrial DNA by at least 25%. | Baseline; up to 3 years |
| 2-Hydroxyglutarate (2-HG) | Will evaluate the percentage change in 2-HG. | Baseline; up to 3 years |
| Amplified DNA junctions | Will evaluate the percentage change in amplified DNA junctions (if applicable). | Baseline; up to 3 years |
| Volume of disease | Will evaluate the percentage change in the volume of disease above a tumor to normal standardized uptake value maximum ratio of 2 from fluorodopa F 18-positron emission tomography. | Baseline; up to 3 years |
| ID | Term |
|---|---|
| D005910 | Glioma |
| ID | Term |
|---|---|
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
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| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D000069439 | Dasatinib |
| C017875 | fisetin |
| D009682 | Magnetic Resonance Spectroscopy |
| D057832 | Watchful Waiting |
| D019370 | Observation |
| D011794 | Quercetin |
| D000077204 | Temozolomide |
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D017063 | Outcome Assessment, Health Care |
| D010043 | Outcome and Process Assessment, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D008722 | Methods |
| D044948 | Flavonols |
| D005419 | Flavonoids |
| D002867 | Chromones |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D007093 | Imidazoles |
| D013812 | Therapeutics |
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